Structural correlates of prestin activity

NIH RePORTER · NIH · R01 · $664,712 · view on reporter.nih.gov ↗

Abstract

With the identification of prestin, an anion transporter (SLC26) family member, as the elusive lateral membrane motor protein of the outer hair cell (OHC), we are faced with the possibility of understanding how this single molecule can effect the mammal’s exquisite sense of hearing. We propose to target a focused set of aims, including 1) determining the role of a leakage conductance in prestin, distinct from its transporter pathway, in hearing and defining its structural basis; 2) determine the role of anion binding residues, and the influence of mechanical load in governing prestin’s frequency dependence; simultaneous measures of sensor charge movement (NLC), electromotility and evoked-forces are planned and 3) determine the structural components of pillars that link prestin to the underlying cytoskeleton, and confirming the importance of such links in hearing. In order to reach these goals, we will employ a host of genetic, electrophysiological, molecular biological and biochemical methods. We believe that the information that we obtain through these studies will aid in understanding how the OHC enables us to hear so well and in turn how we might combat pathologies of the OHC that afflict millions.

Key facts

NIH application ID
9872145
Project number
5R01DC008130-12
Recipient
YALE UNIVERSITY
Principal Investigator
DHASAKUMAR S NAVARATNAM
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$664,712
Award type
5
Project period
2007-01-01 → 2022-02-28